The injectable contraceptive depot medroxy-progesterone acetate (DMPA) (Depo-Provera) is commonly used by women worldwide, and it contains the same progestin that is most commonly used in combined estrogen and progestin hormonal therapy (CHT) regimens taken by postmenopausal women in the United States. Data from several recent studies indicate that CHT increases a woman's risk of breast cancer, and that the progestin component of CHT may be particularly important with respect to this increased risk. There are limited data on the relationship between DMPA and breast cancer risk though. The available evidence suggests that current DMPA use is associated with a 1.5 to 1.65-fold increased risk of breast cancer. However, additional studies of the relationship between DMPA use and breast cancer are needed because these studies had methodologic limitations (sample size and/or study design issues), none were conducted in the U.S. and so it is unclear whether or not these results are generalizable to U.S. women (since reproductive and contraceptive patterns vary widely by country), and little is known about mechanisms through which DMPA promotes breast cancer. This study is worthwhile even if we find that there is no association between DMPA and breast cancer risk, since in this case women using DMPA will be reassured that using the same drug that has been implicated as a cause of breast cancer does not also increase their breast cancer risk when taken as an injectable contraceptive. Herein we propose a case-control study of 1,000 women aged 20-44 who have been diagnosed with breast cancer and 1,000 population-based controls who reside in the Seattle-Puget Sound area. The specific hypotheses to be tested are: (1) Is DMPA use associated with an increased risk of breast cancer in premenopausal women 20-44? Does the duration and/or recency of DMPA use influence the magnitude of this association?; (2) Do demographic, reproductive, or anthropometric characteristics, such as parity and body mass index, modify this association?; and (3) Does the association between DMPA and breast cancer risk vary by histologic type or by the expression of steroid receptors including ERq, ERft, and PR?